rs117920810 (TPT1P9-LINC02578): Childhood Glioma GWAS

Key takeaways

• This variant was examined in the largest multi-ancestry genome-wide association study (GWAS) of childhood glioma conducted at the time, covering 4,069 children with brain tumors and 8,778 controls across six genetic ancestries.
• The study's primary genome-wide significant discovery was at chromosome 9p21.3 - the CDKN2B-AS1 region - not at the TPT1P9-LINC02578 locus where this variant resides.
• Childhood glioma associations were strongest for low-grade astrocytoma, the most common subtype (~80% of pediatric gliomas), and were consistent across all six ancestries studied.
• No genome-wide significant evidence specifically for rs117920810 is present in the provided study materials; any association at this locus should be considered preliminary or unestablished.

What the research says A population-based GWAS meta-analysis examined 4,069 children with glioma (a type of brain tumor) and 8,778 controls across six genetic ancestries, providing the first genome-wide significant evidence for common variant predisposition in pediatric neuro-oncology. The primary finding was at 9p21.3 within the gene CDKN2B-AS1: the lead variant rs573687 was associated with childhood astrocytoma with an odds ratio of 1.273 (95% CI 1.179-1.374) and p-value of 6.974×10^-¹^0, driven by low-grade astrocytoma cases and replicated in an independent cohort. A transcriptome-wide association study additionally linked predicted reduced brain-tissue expression of CDKN2B - a tumor suppressor gene (one that normally restrains uncontrolled cell division) - to astrocytoma risk (p=8.090×10^-8).

Reported associations

• Childhood astrocytoma (study context): The childhood glioma GWAS in which rs117920810 was examined identified a genome-wide significant association at 9p21.3 (rs573687, OR 1.273, p=6.974×10^-¹^0) for astrocytoma overall, driven by low-grade cases; no genome-wide significant signal at the TPT1P9-LINC02578 locus is documented in the provided materials.
• Childhood glioma overall (study context): For glioma regardless of subtype, a separate variant rs3731239 at 9p21.3 approached genome-wide significance (p=5.411×10^-8); high-grade tumors showed no significant association.

Evidence quality The underlying GWAS meta-analysis is methodologically robust - 4,069 cases, 8,778 controls, six genetic ancestries, population-based case ascertainment, and independent replication of the primary finding - making it the most powerful study of common variant predisposition in pediatric glioma published at the time. However, the provided study materials contain no specific p-value, odds ratio, or replication data for rs117920810 at the TPT1P9-LINC02578 locus. Any potential association between this variant and childhood glioma or any other trait must therefore be considered preliminary or absent based on available evidence. The methodological strength of the study's primary findings does not extend to this locus without documented association statistics.

Lifestyle considerations No lifestyle considerations on file for this variant.